Tuesday, December 27, 2016

Is genetics still metaphysical? Part VI. What might lead to a transformative insight in biology today--if we need one

It's easy to complain about the state of the world, in this case, of the life sciences, and much harder to provide the Big New Insights one argues might be due. Senioritis makes it even easier: when my career in genetics began, not very much was known. Genes figuratively had 2 alleles, with measurable rates of recurrence by mutation. Genetically tractable traits were caused by the proteins in these genes; quantitative traits were too complex to be considered seriously to be due to individual genes, so were tacitly assumed to be the additive result of an essentially infinite number of them.

How many genes there were was essentially unknowable, but using identified proteins as a gauge, widely thought to be around 100,000. The 'modern evolutionary synthesis' solved the problem, conceptually, by treating these largely metaphorical causal items as largely equivalent, if distinct, entities whose identities were essentially unknowable. That is, at least, we didn't have to think about them as specific entities, only their collective actions. Mendelian causal genes, evolving by natural selection was, even if metaphorical or even in a serious way metaphysical, a highly viable worldview in which to operate. A whole science enterprise grew around this worldview. But things have changed.

Over the course of my career, we've learned a lot about these metaphysical units. Whether or not they are now more physical than metaphysical is the question I've tried to address in this series of posts, and I think there's not an easy answer--but what we have, or should have, understood is that they are not units! If we have to have a word for them, perhaps it should be interactants. But even that is misleading because the referents are not in fact unitary. For example, many if not most 'genes' are only active in context-dependent circumstances, are multiply spliced, may be post-trascriptionally edited, are chemically modified, and have function only when combined with other units (e.g., don't code for discretely functioning proteins), etc.

Because interaction is largely a trans phenomenon--between factors here and there, rather than just everything here, the current gene concept, and the panselectionistic view in which every trait has an adaptive purpose, whether tacit or explicit, is a serious or even fundamental impediment to a more synthetic understanding. I feel it's worth piling on at this point, and adding that the current science is also pan-statistical in ways that in my view are just as damaging. The reason, to me, is that these methods are almost entirely generic, based on internal comparison among samples, using subjective decision-criteria (e.g., p-values) rather than testing data against a serious-level theory.

If this be so, then perhaps if the gene-centered view of life, or even the gene concept itself as life's fundamental 'atomic' unit, needs to be abandoned as a crude if once important approximation to the nature of life. I have no brilliant ideas, but will try here to present the sorts of known facts that might stimulate some original thinker's synthesizing insight--or, alternatively, might lead us to believe that no such thing is even needed, because we already understand the relevant nature of life: that as an evolutionary product it is inherently not 'regular' the way physics and chemistry are. But if our understanding is already correct, then our public promises of precision medicine are culpably misleading slogans.

In part V of this series I mentioned several examples of deep science insight, that seemed to have shared at least one thing in common: they were based on a synthesis that unified many seemingly disparate facts. We have many facts confronting us. How would or might we try to think differently about them? One way might be to ask the following questions: What if biological causation is about difference, not replication? What if 'the gene' is misleading, and we were to view life in terms of interactions rather than genes-as-things? How would that change our view?

Here are some well-established facts that might be relevant to a new, synthetic rather than particulate view of life:

1. Evolution works by difference, not replication Since Newton or perhaps back to the Greek geometers, what we now call 'science' largely was about understanding the regularities of existence. What became known as 'laws' of Nature were, initially for theological reasons, assumed to be the basis of existence. The same conditions led to the same outcomes anywhere. Two colliding billiard balls here on Earth or in any other galaxy, would react in identical ways (yes, I know, that one can never have exactly the same conditions--or billiard balls--but the idea is that the parts of the cosmos were exchangeable.) But one aspect of life is that it is an evolved chemical phenomenon whose evolution occurred because elements were different rather than exchangeable. Evolution and hence life, is about interactions or context-specific relative effects (e.g., genetic drift, natural selection).

2. Life is a phenomenon of nested (cladistic) tree-like relationships Life is not about separated, independent entities, but about entities that from the biosphere down (at least) to individual organisms are made of sets of variations of higher-level components. Observation at one level, at least from cells up to organs to systems to individuals, populations, species and ecosystems, are reflections of the nested level(s) the observational level contains.

3. Much genetic variation works before birth or on a population level Change may arise by genetic mutation, but function is about interactions, and success--which in life means reproduction--depends on the nature of the interactions at all levels. That is, Darwinian competition among individuals of different species is only one, and perhaps one of the weakest, kinds of such interaction. Embryonic development is a much more direct, and stronger arena for filtering interactions, than competition (natural selection) among adults for limited resources. In a similar way, some biological and even genetic factors work only in a population way (bees and ants are an obvious instance, as are bacterial microfilm and the life cycles of sponges or slime molds).

4. Homeostasis is one of the fundamental and essential ways that organisms interact Homeostasis as an obvious example of a trans phenomenon. It's complexly trans because not only do gene-expression combinations change, but they are induced to change by extra-cellular and even extra-organismal factors both intra and inter-species. The idea of a balance or stasis, as with organized and orchestrated combinatorial reaction surely cannot be read of in cis. We have known about interactions and reactions and so on, so this is not to invoke some vague Gaia notions, but to point out the deep level of interactions, and these depend on many factors that themselves vary, etc.

5. Environments include non-living factors as well as social/interaction ones No gene is an island, even if we could identify what a 'gene' was, and indeed that no gene stands alone is partly why we can't. Environments are like the celestial spheres: from each point of view everything else is the 'environment', including the rest of a cell, organ, system, organism, population, ecosystem. In humans and many other species, we must include behavioral or social kinds of interactions as 'environment'. There is no absolute reference frame in life any more than in the cosmos. Things may appear linear from one point of view, but not another. The 'causal' effects of a protein code (a classical 'gene') depend on its context--and vice versa.

6. The complexity of factors often implies weak or equivalent causation--and that's evolutionarily fundamental. Factors or 'forces' that are too strong on their own--that is, that appear as individually identifiable 'units'--are often lethal to evolutionary survival. Most outcomes we (or evolution) care about are causally complex, and they are always simultaneously multiple: a species isn't adapting to just one selective factor at a time, for example. Polygenic causation (using the term loosely to refer to complex multi-factoral causation) is the rule. These facts mean that individually identified factors usually have weak effects and/or that there are alternative ways to achieve the same end, within or among individuals. Selection, even of the classical kind, must be typically weak relative to any given involved factor.

7. The definition of traits is often subjective and affects their 'cause' Who decides what 'obesity', 'intelligence', or 'diabetes' is? In general, we might say that 'Nature' decides what is a 'trait', but in practice it is often we, via our language and our scientific framework, who try to divide up the living world into discrete categories and hence to search for discrete causal factors. It is no surprise that what we find is rather arbitrary, and gives the impression of biological causation as packaged into separate items rather than being fundamentally about a 'fabric' of interactions. But the shoehorn is often a major instrument in our causal explanations.

8. The 'quantum mechanics' effect: interaction affects the interactors In many aspects of life, obviously but not exclusively applied to humans, when scientists ask a question or publicize a result, it affects the population in question. This is much like the measurement effect in quantum mechanics. Studying something affects it in ways relevant to the causal landscape we are studying. Even in non-human life, the 'studying' of rabbits by foxes, or of forests by sunlight, affects what is being studied. This is another way of pointing out the pervasive centrality of interaction. Just like political polls, the science 'news' in our media, affect our behavior and it is almost impossible to measure the breadth and impact of this phenomenon.

All of these phenomena can be shoe-horned into the 'gene' concept or a gene-centered view of life or of biomedical 'precision'. But it's forced: each case has to be treated differently, by statistical tests rather than a rigorous theory, and with all sorts of exceptions, involving things like those listed here, that have to be given post hoc explanations (if any). In this sense, the gene concept is outmoded and an overly particulate and atomized view of a phenomenon--life--whose basic nature is that it is not so particularized.

Take all of these facts, and many others like them, and try to view them as a whole, and as a whole that, nonetheless can evolve. Yesterday's post on how I make doggerel was intended to suggest a similar kind of mental exercise. There can be wholes, and they can evolve, but they do it as wholes. If there is a new synthesis to be found, my own hunch it would be in these sorts of thoughts. As with the examples I discussed a few days ago (plate techtonics, evolution itself, and relativity), there was a wealth of facts that were not secret or special, and were well-known. But they hadn't been put together until someone thinking hard about them, who was also smart and lucky, managed it. Whether we have this in the offing for biology, or whether we even need it, is what I've tried to write about in this series of posts.

Of course, one shouldn't romanticize scientific 'revolutions'. As I've also tried to say, these sorts of facts, which are ones I happen to have thought of to list, do not in any way prove that there is a grand new synthesis out there waiting to be discovered. It is perfectly plausible that this kind of ad hoc, chaotic view of life is what life is like. But if that's the case, we should shed the particulate, gene-centered view we have and openly acknowledge the ad hoc, complex, fundamentally trans nature of life--and, therefore, of what we can promise in terms of health miracles.

3 comments:

I neglected to add a thanks to Michael Joyner for suggesting that homeostasis be in a list of relevant phenomena. It is a, if not by far the, most important examples of the fundamentally 'trans' nature of life, and occurs all the time and at many levels of gene action.

Great post, Ken. As you probably know, you are in (implicit) conversation with so much of contemporary feminist science studies (Sarah Richardson, Evelyn Fox Keller, Karen Barad). Your question about whether genetics is still "metaphysical" brings me right back to Waddington's comments at Serbelloni, about the impact of "some metaphysical concepts" on his work as a geneticist. I am coming in late on this, but look forward to reading the previous five (!) posts, and to re-following this really enjoyable blog. And to seeing both of you in the New Year.

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